The overall objective of the proposed research is the development of noninvasive definitive means for diagnostic detection and differentiation of specific types of myocardial pathology in vivo based on quantitative ultrasonic characterization of the tissue itself, as opposed to assessment of dimensions or motion. The underlying hypothesis is that morphologic changes in myocardium alter the physical properties of the tissue, and that these alterations can be quantified with indexes based on frequency- dependent ultrasonic backscatter. Studies will be performed to delineate: 1) the sensitivity and specificity of quantitative ultrasonic integrated backscatter for detection of progressive interstitial fibrosis resulting from chronic aortic regurgitation, induced experimentally in dogs or occurring in patients evaluated also with conventional echocardiography; and 2) the utility of tissue characterization with ultrasound in the longitudinal assessment of development of interstitial edema and cellular infiltration resulting from graft rejection after cardiac transplantation in patients. Ultrasonic measurements in animals and humans will be obtained under closed-chest conditions with a novel system developd in our laboratory that interfaces acquisition of real-time quantitative ultrasonic integrated backscatter and conventional echocardiography. The concept that fibrosis, water accumulation, and inflammatory responses in myocardium can be detected by quantitative ultrasound is based on an extensive body of work from our group and other. Results should broaden the diagnostic and quantitative power of ultrasound by permitting noninvasive detection and quantification of myocardial injury in patients based on tissue characterization of myocardium.